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Leveraging bile solubilization of poorly water-soluble drugs by rational polymer selection
Please always quote using this URN: urn:nbn:de:bvb:20-opus-296957
- Poorly water-soluble drugs frequently solubilize into bile colloids and this natural mechanism is key for efficient bioavailability. We tested the impact of pharmaceutical polymers on this solubilization interplay using proton nuclear magnetic resonance spectroscopy, dynamic light scattering, and by assessing the flux across model membranes. Eudragit E, Soluplus, and a therapeutically used model polymer, Colesevelam, impacted the bile-colloidal geometry and molecular interaction. These polymer-induced changes reduced the flux of poorlyPoorly water-soluble drugs frequently solubilize into bile colloids and this natural mechanism is key for efficient bioavailability. We tested the impact of pharmaceutical polymers on this solubilization interplay using proton nuclear magnetic resonance spectroscopy, dynamic light scattering, and by assessing the flux across model membranes. Eudragit E, Soluplus, and a therapeutically used model polymer, Colesevelam, impacted the bile-colloidal geometry and molecular interaction. These polymer-induced changes reduced the flux of poorly water-soluble and bile interacting drugs (Perphenazine, Imatinib) but did not impact the flux of bile non-interacting Metoprolol. Non-bile interacting polymers (Kollidon VA 64, HPMC-AS) neither impacted the flux of colloid-interacting nor colloid-non-interacting drugs. These insights into the drug substance/polymer/bile colloid interplay potentially point towards a practical optimization parameter steering formulations to efficient bile-solubilization by rational polymer selection.…
Author: | Jonas SchlauersbachORCiD, Simon Hanio, Bettina Lenz, Sahithya P. B. Vemulapalli, Christian Griesinger, Ann-Christin Pöppler, Cornelius Harlacher, Bruno Galli, Lorenz Meinel |
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URN: | urn:nbn:de:bvb:20-opus-296957 |
Document Type: | Journal article |
Faculties: | Fakultät für Chemie und Pharmazie / Institut für Organische Chemie |
Fakultät für Chemie und Pharmazie / Institut für Pharmazie und Lebensmittelchemie | |
Language: | English |
Parent Title (English): | Journal of Controlled Release |
Year of Completion: | 2021 |
Edition: | Accepted Version |
Volume: | 330 |
Pagenumber: | 36-48 |
Source: | Journal of Controlled Release (2020) 330, 36-48. https://doi.org/10.1016/j.jconrel.2020.12.016 |
DOI: | https://doi.org/10.1016/j.jconrel.2020.12.016 |
Sonstige beteiligte Institutionen: | Max Planck Institute for Biophysical Chemistry, Am Faßberg 11, DE-37077 Goetingen, Germany |
Sonstige beteiligte Institutionen: | Novartis Pharma AG, Lichtstrasse 35, CH-4056 Basel, Switzerland |
Sonstige beteiligte Institutionen: | Helmholtz Institute for RNA-based Infection Biology (HIRI), Josef-Schneider-Straße 2/D15, DE-97080 Wuerzburg, Germany |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 547 Organische Chemie |
Tag: | bile salt; colloid; flux; polymer drug interaction; simulated intestinal fluid |
Release Date: | 2022/12/17 |
Licence (German): | CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International |